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| 1 | Effects of fatty acid regulation on visfatin gene expression in adipocytes显示文摘Background The levels of long-term elevated serum or intracellular free fatty acid (FFA) induce insulin resistance associated with central obesity. The insulin-mimetic protein visfatin is preferentially produced by visceral adipose tissues and has been implicated in obesity and insulin resistance. To identify that FFA is capable of inducing insulin resistance and to clarify the role of FFA on visfatin, we examined the effect of monounsaturated FFA oleate (C18:1) and saturated FFA palmitate (C16:0) on glucose transport and visfatin gene expression in cultured 3T3-L1 adipocytes or preadipocytes. Methods FFA-free DMEM/F12, 0.125 mmol/L, 0.5 mmol/l and 1.0 mmol/L oleate or palmitate was added to cultured 3T3-L1 adipocytes or preadipocytes and incubated overnight. Glucose transport was assessed as 3H- 2-deoxy-glucose uptake. Total RNA was extracted and subjected to RT-PCR for the measurement of visfatin mRNA levels. Statistical comparisons between control group and other groups were performed with the two-tailed paired t test, and one-way ANOVA was used to compare the mean values among the groups. Results Insulin increased specific membrane glucose transport in 3T3-L1 preadipocytes. Upregulation was evident from 15 minutes to 1 hour exposure to insulin. However, after 6-hour exposure to insulin, there was a downregulation in the response to insulin. Dose response studies demonstrated that 2-deoxy glucose transport was increased by 336% at 50 nmol/L insulin (P<0.01), and reached a maximal effect at 100 nmol/L insulin (P<0.01). Oleate and palmitate treatment did not influence basal glucose transport (without insulin stimulation), whereas insulin-stimulated glucose transport was inhibited after overnight oleate and palmitate treatment in preadipocytes and adipocytes. In 3T3-L1 preadipocytes, insulin resistance could be achieved at 0.125 mmol/L oleate or palmitate (P<0.05, respectively), and the inhibition was dose dependent. In adipocytes, the inhibition was noted at 0.5 mmol/L oleate or 1.0 mmol/L palmitate. Visfatin mRNA expression increased during differentiation more than 1.5-fold. Bovine serum albumin (BSA) did not influence visfatin mRNA expression compared with the control group. Dose-response studies demonstrated that addition of 0.125 mmol/L oleate and palmitate to 3T3-L1 adipocytes decreased visfatin mRNA expression significantly (78%, 77%, respectively, relative to untreated control, P<0.05), and further to 65% (relative to untreated control, P<0.05) and 55% (relative to untreated control, P<0.01) at 1.0 mmol/L FFA. Furthermore, the suppression on preadipocytes was similar to that of adipocytes, which reached a maximal reduction of 44% (oleate, P<0.05) and 47% (palmitate, P<0.05) at 1.0 mmol/L FFA.Conclusions Oleic acid and palmitic acid mayinduce insulin resistance in 3T3-L1 adipocytesand preadipocytes. Downregulation of visfatinmRNA may contribute to impair insulinsensitivity caused by oleate and palmitate. | WEN Yu WANG Hong-wei WU Jing LU Hui-ling HU Xiu-fen Katherine Cianflone | 2006 | Chinese Medical Journal2006,,20: | 22 |
| 2 | 促酰化蛋白(ASP)诱导3T3-L1前脂肪细胞分化显示文摘促酰化蛋白 (ASP)代替经典激素“鸡尾酒”诱导法中胰岛素 ,通过形态学观察、油红染色分化百分比测定、脂肪细胞甘油三酯合成率和甘油三酯总量测定 ,并与经典激素“鸡尾酒”法诱导前脂肪细胞分化情况比较 ,探讨ASP是否具有诱导 3T3 L1前脂肪细胞分化作用 .ASP组诱导分化第 6d ,3T3 L1前脂肪细胞变大、变圆 ,出现大量脂肪滴 ,形态由前脂肪细胞向成熟脂肪细胞转变 ;随着诱导分化时间延长 ,胞浆中脂滴进一步积累 .分化 9d时 ,3T3 L1前脂肪细胞分化完全 .油红染色结果显示 ,ASP组分化率很高 (85 % ) ,与胰岛素组分化率 (90 % )相似 ,明显高于IBMX +DEX组 (4 0 % ) .ASP不仅促进 3T3 L1前脂肪细胞形态向成熟脂肪细胞转化 ,同时促进细胞中甘油三酯的合成和积累 .ASP组诱导分化第 3d时 ,脂肪细胞甘油三酯合成率明显高于对照组和IBMX +DEX组 ,但仍低于胰岛素组 ;在分化第 6d和第 9d时 ,ASP组甘油三酯合成率进一步升高 ,与对照组和IBMX +DEX组相比差异有极显著性 ,与胰岛素组相比无显著性差异 .ASP组诱导分化 3d时 ,脂肪细胞中甘油三酯总量明显高于对照组和IBMX +DEX组 ;分化 6d和 9d时 ,甘油三酯总量进一步升高 ,与对照组和IBMX +DEX组相比差异有极显著性 ,而与胰岛素组相比无显著性差异 .结果表明 。 | 卢慧玲 王宏伟 Katherine CIANFLONE 林汉华 | 2004 | 中国生物化学与分子生物学报2004,20,3: | 14 |
| 3 | 2型糖尿病患者和甲状腺疾病患者血浆脂联素水平变化显示文摘在肥胖型糖尿病、非肥胖 2型糖尿病、甲亢、甲减和正常对照 5组病例测定空腹血脂联素、甲状腺激素、胰岛素等指标。结果显示,脂联素与体重指数、血脂及FT4 密切相关。糖尿病人群脂联素与体重指数比胰岛素更相关。 | 张木勋 杨雁 Katherine Cianflone 余海英 张建华 王宏伟 卢慧玲 | 2005 | 中华内分泌代谢杂志2005,21,1: | 13 |
| 4 | The Role of High-sensitivity C-reactive Protein, Interleukin-6 and Cystatin C in Ischemic Stroke Complicating Atrial Fibrillation显示文摘This study examined the role of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and cystatin C in ischemic stroke complicating atrial fibrillation (AF) and the relationship of systemic inflammation with this disease in order to identify AF patients who are at high risk of stroke and need optimal anticoagulant therapy.A total of 103 AF patients, simple (n=75) or complicated by ischemic stroke (n=28), and 112 control subjects were recruited.IL-6 level was detected by using enzyme linked immunosorbent assay.Cystatin C and hsCRP levels were measured by means of a particle-enhanced immunonephelometric assay.The results showed that the AF patients had higher levels of hsCRP (P=0.004), IL-6 (P=0.000), and cystatin C (P=0.000) than control subjects.Plasma hsCRP level was increased in the AF patients with ischemic stroke as compared to the patients with simple AF (P=0.036).The AF patients who had the level of hsCRP exceeding 3.83 mg/L were at a higher risk than those with hsCRP level lower than 3.83 mg/L (P=0.030).After adjusting for other factors, cystatin C remained positively associated with IL-6 (r=0.613) and hsCRP (r=0.488).It was concluded that hsCRP is positively correlated with ischemic stroke complicating AF and may be a risk factor independent of other risk factors for AF.Elevated cystatin C level is also indicative of the increased risk of AF. | 尤玲 汪培华 吕家高 Katherine Cianflone 汪道文 赵春霞 | 2010 | Journal of Huazhong University of Science and Technology(Medical Sciences)2010,30,5: | 13 |
| 5 | 肥胖症儿童血浆脂联素、促酰化蛋白水平变化的临床意义显示文摘目的 探讨血浆脂联素和促酰化蛋白 (ASP)水平与儿童肥胖症发病的关系。方法 研究对象共 12 1名 ,年龄 2~ 6岁 ,男 62名 ,女 5 9名 ,其中肥胖儿童 62名 ,正常对照儿童 5 9名。采用ELISA方法检测血浆脂联素、ASP水平。结果 (1)肥胖儿童血浆脂联素低于正常对照组 (P <0 .0 5 ) ;ASP高于正常对照组〔(98.4± 2 8.0 )nmol/Lvs (68.9± 3 5 .9)nmol/L ,P <0 .0 1〕。不同性别血浆脂联素、ASP水平差异无显著性 ;(2 )肥胖儿童的血脂各指标与正常对照组相比 ,差异无显著性 ;(3 )相关性分析 :脂联素与BMI呈负相关 (r =-0 .3 5 ,P <0 .0 5 ) ,与甘油三酯呈负相关 (r =-0 .5 1,P <0 .0 1) ,与其他血脂指标无相关性 ;ASP与BMI呈正相关 (r =0 .5 1,P <0 .0 1) ,除与游离脂肪酸呈正相关外 (r =0 .67,P <0 .0 1) ,与其它血脂指标无相关性。结论 在儿童肥胖症中 ,脂源性激素脂联素和ASP在血脂异常之前即有显著性变化。测定血浆脂联素和ASP水平为儿童肥胖症的防治提供新的检测指标。 | 卢慧玲 王宏伟 Katherine Cianflone 温宇 林汉华 | 2004 | 中华内分泌代谢杂志2004,20,6: | 7 |
| 6 | 肾脏疾病儿童血浆促酰化蛋白水平测定的意义显示文摘目的探讨肾脏疾病儿童血浆促酰化蛋白(ASP)与血浆C3、非酯化脂肪酸(NEFA)及血脂的关系。方法肾脏疾病组48例,健康对照组279例。将48例肾脏疾病儿童分为3组:1.急性链球菌感染后肾小球肾炎(APSGN)组12例;2.狼疮性肾炎(LN)组4例;3.肾病综合征(NS)组32例。用ELISA方法检测各组血浆ASP水平,酶学比色法测定其NEFA水平,用酶学比浊法检测其血浆C3、血脂等生化指标。数据采用GraphPad Prism 4.0软件进行统计学分析。结果1.APSGN组(81.8±24.8)nmol/L、LN组(90.9±28.2)nmol/L和NS组(101.4±39.9)nmol/L血浆ASP水平明显高于健康对照组[(44.3±25.2)nmol/LPa<0.01];APSGN和LN组血浆C3水平均低于健康对照组(Pa<0.05),NS组与健康对照组比较C3无明显变化。2.肾脏疾病各组存在一定程度血脂代谢紊乱。APSGN组血浆三酰甘油(TG)水平高于健康对照组,但无统计学差异(P>0.05),而高密度脂蛋白胆固醇(HDL-C)显著低于健康对照组(P<0.001)。LN和NS组存在显著高TG、高TC和高低密度脂蛋白胆固醇(LDL-C)血症,LN组患儿还存在低血浆HDL-C水平(P<0.001),载脂蛋白(Apo)A和ApoB升高仅见于NS组(P<0.01,0.001);各组NEFA水平无显著变化。3.肾脏疾病患儿血浆ASP水平与TG(r=0.301P<0.05)、ApoA(r=0.307P<0.05)、C3(r=0.30P<0.03)均呈正相关。补体C3与TC(r=0.479P<0.001)、LDL-C(r=0.376P<0.01)、HDL-C(r=0.447P<0.01)、ApoA(r=0.551P<0.001)、ApoB(r=0.365P<0.01)均呈正相关。结论脂源性激素ASP和补体C3参与肾脏疾病患儿血脂代谢的调节。ASP的升高发生在严重血脂紊乱之前。 | 唐锦辉 温宇 王宏伟 Katherine Cianflone 米杰 | 2008 | 实用儿科临床杂志2008,23,5: | 6 |
| 7 | 诱导SW872前脂肪细胞分化的最优方法探讨显示文摘目的探讨诱导SW872脂肪细胞分化的最优方法。方法根据不同的分化诱导刺激分为6组:①对照组:无分化刺激,仅有DMEM/F12培养基;②胰岛素组:含2 mg/L Insulin;③1-甲基3-异丁基黄嘌呤组:含0.5 mmol/L IBMX;④促酰化蛋白组:含50 mg/L ASP;⑤激素鸡尾酒(胰岛素+1-甲基3-异丁基黄嘌呤+地塞米松组:含2 mg/L insulin+0.5 mmol/L IBMX+1.0μmol/L DEX;⑥油酸(oleic acid)组:含0.2 mg/L oleic acid。通过形态学观察、油红染色、测定细胞甘油三酯总量的方法。结果多组分化刺激中,油酸组刺激可在24 h内诱导SW872细胞分化,而且分化均匀,分化率高,分化后形成的脂肪细胞形态典型;而且油酸组促进SW872细胞分化过程中细胞内甘油三酯的积累。结论油酸是诱导SW872细胞分化的最佳方法,该方法的建立和统一,为进一步利用SW872细胞进行脂代谢、脂肪细胞功能的研究奠定了基础。 | 卢慧玲 王宏伟 Katherine Cianflone 温宇 | 2006 | 基础医学与临床2006,26,3: | 5 |
| 8 | 促酰化蛋白诱导前脂肪细胞分化过程中DGAT、LPL、adipsin mRNA表达显示文摘目的观察促酰化蛋白(acylation sti mulating protein,ASP)诱导3T3-L1前脂肪细胞的分化过程中,脂肪特异性的功能酶脂蛋白脂酶(LPL)、二酰基甘油转酰酶(DGAT)以及脂肪细胞特异性功能蛋白adipsin表达的时序性和强度。方法以3T3-L1前脂肪细胞为实验对象,用ASP代替经典激素鸡尾酒诱导刺激中的胰岛素,诱导3T3-L1前脂肪细胞分化,分别在诱导分化1、2、4、6、8d收获细胞,采用RT-PCR法检测分化过程中LPL、DGAT和adipsin的mRNA表达情况。结果在ASP诱导3T3-L1前脂肪细胞分化过程中,LPL、DGAT、adipsin mRNA表达逐渐升高,其中LPL mRNA表达最早,在分化1d时就有低水平的表达,分化2d时出现DGAT mRNA的表达,并随着脂肪细胞的进一步分化成熟,LPL和DGAT mRNA表达水平逐步升高,持续到分化终末期;adipsin mRNA表达出现最晚,在分化4d时才有表达,随后其表达水平急剧升高,持续到分化终末期。结论ASP诱导3T3-L1前脂肪细胞分化过程中,按照一定的时序性依次诱导脂肪特异性的功能酶LPL、DGAT和功能蛋白adipsin的mRNA表达,是脂肪细胞生物学功能成熟的重要物质基础,同时也是ASP诱导前脂肪细胞分化的分子机制之一。 | 王宏伟 卢慧玲 温宇 Katherine Cianflone | 2005 | 华中科技大学学报(医学版)2005,34,6: | 5 |
| 9 | 促酰化蛋白受体C5L2在前脂肪细胞分化过程和脂肪酸负荷下的表达研究显示文摘目的观察3T3-L1前脂细胞分化和游离脂肪酸(FFA)对3T3-L1(前)脂肪细胞 C5L2基因和蛋白表达的影响。方法采用逆转录(RT)-PCR 和流式细胞仪检测不同分化时段和 FFA 处理后(前)脂肪细胞 C5L2 mRNA 和蛋白表达。结果 3T3-L1脂肪细胞 C5L2 mRNA 表达呈分化依赖性增加,而 C5L2蛋白表达水平在分化早期显著增强,诱导分化6h C5L2蛋白表达增加了21%(61%±18% vs 51%±15%,P<0.05);分化12h 达高峰,增加了38%(70%±12%vs 51%±15%,P<0.01);分化3d 基本恢复至0d 水平。在3T3-L1成熟脂肪细胞,0.5 mmol/L 和1.0 mmol/L 油酸分别抑制46%(0.58±0.21 vs 1.08±0.46,P70.05)和84%(0.18±0.04 vs 1.08±0.46,P<0.05)C5L2 mRNA 表达,而0.125 mmol/L 油酸即能显著下调36%(35%±8% vs 54%±7%,P<0.01)C5L2蛋白表达。低浓度棕榈酸均能明显抑制 C5L2 mRNA 和蛋白的表达,1.0mmol/L 时 C5L2 mRNA和蛋白表达分别减少了41%(0.57±0.28 vs 0.97±0.41,p<0.05)和55%(24%±13% vs 54%±7%,P<0.01)。油酸和棕榈酸对前脂肪细胞 C5L2表达差异无统计学意义。结论促酰化蛋白/C5L2途径参与了脂肪细胞分化的调控过程。C5L2 mRNA 和蛋白表达的下调可能参与了油酸和棕榈酸诱导的成熟脂肪细胞胰岛素抵抗的发生。 | 温宇 王宏伟 吴静 卢慧玲 夏治 Katherine Cianflone | 2007 | 中华医学杂志2007,87,36: | 5 |
| 10 | 2型糖尿病患者血浆脂联素水平及其影响因素显示文摘目的 了解2型糖尿病患者血浆脂联素水平与体重指数(BMI)、血浆胰岛素水平、游离脂肪酸(FFA)及血脂的相关性。方法 根据BMI水平将51名2型糖尿病患者分为肥胖2型糖尿病组(BMI≥25kg/m2)、正常体重2型糖尿病组,将28名正常体重非糖尿病者设为对照组。以ELISA法测定脂联素和FFA,化学发光法测定空腹胰岛素(FINS),同时测定空腹血糖(FPG)、餐后2 h血糖(2HPG)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C),计算低密度脂蛋白胆固醇(LDL-C)和胰岛素抵抗指数(HOMA-IR)。结果 肥胖2型糖尿病组脂联素水平显著低于非肥胖2型糖尿病组和对照组(P<0.05),后两组脂联素水平无差异。单因素相关分析显示脂联素与BMI及TG负相关,相关系数分别为-0.3459(P<0.01)和-0.3603(P<0.01),与FFA等无相关性。包括年龄、BMI、HDL-C、LDL-C、TG、TC、FPG、FINS、FFA和HOMA-IR的多因素回归分析显示,BMI和TG对脂联素的影响相当。结论 不同BMI个体的脂联素水平具有差异,在正常BMI范围内的2型糖尿病患者与非糖尿病者血浆脂联素水平差异无显著性。胰岛素抵抗程度对脂联素无明显影响。TG和BMI是一组很好的评估脂联素水平和作用的指标。 | 杨雁 张木勋 Katherine Cianflone 余海英 张建华 王宏伟 卢慧玲 | 2004 | 华中科技大学学报(医学版)2004,33,1: | 4 |
| 11 | Abnormal Adipokines Associated with Various Types of Obesity in Chinese Children and Adolescents显示文摘Objective To explore the role of adipokines including insulin, resistin, leptin, adiponectin, acylation stimulating protein (ASP) and complement C3 (C3) in various types of obesity (peripheral obesity, abdominal obesity and mixed obesity) in Chinese children and adolescents, and their relationships with body size and pubertal development. Methods Children and adolescents (n=3 508) aged 6 to 18 years, with 1 788 boys and 1 720 girls were assessed for body mass index, waist circumference, pubertal development, blood insulin, resistin, leptin, adiponectin, ASP and C3 levels. Three types of obesity [peripheral obesity (n=43), abdominal obesity (n=473), mixed obesity (n=1 187)] and non‐obese control (n=1 805) were defined with combined use of Chinese body mass index and waist circumference criteria. Results Serum resistin, leptin and adiponectin levels were higher in girls than those in boys (all P<0.01). Insulin and leptin increased and adiponectin decreased across five Tanner stages in both girls and boys (all P<0.001), while ASP changed only in girls (P<0.001) and C3 only in boys (P<0.001). Insulin, leptin and ASP were higher, but adiponectin was lower in all three types of obesity vs. the non‐obese control (all P<0.05). The greatest abnormalities of all six adipokines were found in the mixed obesity group. With inclusion of body mass index and waist circumference in simultaneous regression analyses, both body size indices were independently and significantly correlated with insulin, leptin and adiponectin after age and gender adjustment. Compared with waist circumference, the body mass index was stronger in interpreting insulin, leptin, adiponectin and ASP levels, whereas it was weaker in explaining variance of plasma C3. Conclusions Obese children have a worse metabolic profile with high insulin, resistin, leptin, ASP and C3, and low adiponectin levels. The adipokine profile in mixed obesity is worse than that in peripheral or abdominal obesity. Identification of obese subjects with a malignant adipokine profile using a combination of body mass index and waist circumference is important for the prevention of obesity‐related disease. | ZHANG MeiXian ZHAO XiaoYuan LIMing CHENG Hong HOU DongQing WEN Yu Katherine CIANFLONE MI Jie | 2011 | Biomedical and Environmental Sciences2011,24,1: | 4 |
| 12 | 多囊卵巢综合征患者血浆酰化刺激蛋白水平变化与血脂相关性研究显示文摘目的探讨多囊卵巢综合征(PCOS)患者血浆中酰化刺激蛋白(ASP)、补体C3、C反应蛋白(CRP)与血脂紊乱的相关性。方法34例PCOS患者分为肥胖组(15例)和非肥胖组(19例),41例年龄匹配月经正常的妇女分为单纯肥胖组(21例)和正常对照组(20名),测定血中ASP、C3、CRP、游离脂肪酸(FFA)、甘油三酯(TG)和总胆固醇(TC)水平。结果肥胖PCOS组、非肥胖PCOS组及单纯肥胖组ASP水平均显著高于正常对照组[分别为(36.4±10.9,34.8±9.9,35.1±14.0,24.8±7.8)nmol/L,均P〈0.05]。肥胖PCOS组及单纯肥胖组C3水平显著高于正常对照组[分别为(2.2±1.2,2.5±1.5,1.1±0.7)g/L,P〈0.05]。肥胖PCOS组、非肥胖PCOS组及单纯肥胖组CRP水平均显著高于正常对照组[分别为(32.1±29.2,30.0±24.8,23.8±5.5,7.5±4.8)mg/L,P〈0.05]。相关分析结果显示,ASP、C3与体重指数(BMI)、CRP、FFA、TG呈显著正相关。CRP与BMI、FFA、TG、TC呈显著正相关。结论PCOS患者存在ASP、C3和CRP水平的异常且与脂质代谢紊乱有关。ASP与C3不相关提示C3在向ASP转化中还受其他因素调节。 | 吴玉文 张木勋 张建华 王宏伟 温宇 Katherine Cianflone | 2008 | 中华内分泌代谢杂志2008,24,5: | 4 |
| 13 | 血浆促酰化蛋白水平与儿童青少年肥胖和代谢综合征的关联性分析显示文摘目的探讨儿童青少年血浆促酰化蛋白(ASP)水平与肥胖及代谢综合征(MS)的关系。方法以2004年北京市儿童青少年代谢综合征(BCAMS)调查总样本中1603名6~18岁儿童青少年为研究对象。采用中国肥胖问题工作组推荐的标准诊断超重和肥胖。符合下述5项指标中的3项及以上者诊断为MS:①腹型肥胖(腰围≥P90);②高血压(≥P90);③高密度脂蛋白胆固醇≤1.03mmol.L-1;④三酰甘油≥1.24mmol.L-1;⑤高空腹血糖(≥5.60mmol.L-1)。采用ELISA法检测血浆ASP水平,免疫透射比浊法检测补体3(C3)水平。采用方差分析比较超重、肥胖及MS儿童青少年的血浆ASP水平,多因素Logistic回归分析血浆ASP水平与超重、肥胖及MS的关系。结果1603名研究对象中男性873名(54.5%)、女性730名(45.5%);超重和肥胖者分别为291名(18.2%)和709名(44.2%);MS为376名(23.4%)。正常体重、超重和肥胖组MS检出率分别为2.2%(13/603名)、15.5%(45/291名)和44.9%(318/709名)。正常体重组血浆ASP水平男性低于女性,差异有统计学意义(t=2.527,P<0.05)。正常体重、超重和肥胖组血浆ASP的几何均值(P25~P75),男性分别为37.52(22.36~64.58)、57.88(34.10~95.11)和60.63(35.30~109.72)nmol.L-1;女性分别为44.16(27.27~74.72)、60.25(35.68~113.15)和66.68(44.56~113.97)nmol.L-1,均呈逐渐升高趋势(男性:F=34.329,P<0.001;女性:F=22.246,P<0.001)。C3水平仅在肥胖女性中升高(P<0.01)。血浆ASP水平随MS组分聚集的数目增加而升高(男性:F=16.422,P<0.001;女性:F=9.661,P<0.001),与高血压、腹型肥胖和高空腹血糖的关系尤为密切。血浆ASP水平升高与儿童青少年超重、肥胖和MS的患病风险密切相关,相对于最低5分位值,位于最高5分位值的ASP水平与超重、肥胖和MS关系的OR值(95%CI)分别为3.90(2.38~6.39)、6.05(4.06~9.01)和2.89(1.93~4.33)。结论超重、肥胖和MS儿童青少年血浆ASP水平明显升高,血浆ASP水平可能对儿童青少年超重、肥胖和MS的发生具有较好的预测价值。 | 张美仙 赵小元 温宇 王宏伟 Cianflone Katherine 程红 侯冬青 米杰 | 2009 | 中国循证儿科杂志2009,4,5: | 4 |
| 14 | 脂肪酸诱导脂肪细胞促酰化蛋白抵抗及机制研究显示文摘目的:观察不同浓度单不饱和脂肪酸(油酸)和饱和脂肪酸(棕榈酸)对3T3-L1(前)脂肪细胞葡萄糖转运的影响,探讨高游离脂肪酸(FFA)负荷在促酰化蛋白(ASP)抵抗形成中的意义,及FFA诱导的3T3-L1(前)脂肪细胞ASP抵抗的机制。方法:体外培养3T3-L1细胞,诱导细胞分化,用不同浓度FFA作用于3T3-L1(前)脂肪细胞,孵育过夜后收获细胞,采用2-脱氧-[3H]-D-葡萄糖掺入法,观察3T3-L1成熟脂肪细胞和前脂肪细胞基础状态和ASP刺激状态的葡萄糖摄取率;采用Western blotting法检测基础状态和ASP刺激的鸟苷酸结合蛋白alpha-q/11(Gαq/11),鸟苷酸结合蛋白beta(Gβ),磷酸化蛋白激酶Calpha(p-PKCα)和磷酸化蛋白激酶Czeta(p-PKCζ)蛋白表达。结果:ASP刺激后,3T3-L1成熟脂肪细胞和前脂肪细胞葡萄糖摄取率分别是基础状态的1.98倍(P<0.01)和2.87倍(P<0.01)。低浓度FFA不影响ASP刺激的葡萄糖转运;而1.0mmol/L时油酸组和棕榈酸组ASP刺激的成熟脂肪细胞葡萄糖摄取率分别减少47%(P<0.05)和34%(P<0.05),前脂肪细胞葡萄糖摄取率分别减少43%(P<0.05)和62%(P<0.01)。1.0mmol/L油酸和棕榈酸抑制成熟脂肪细胞基础状态和ASP刺激的Gβ、Gαq/11、p-PKCα和p-PKCζ蛋白表达,油酸组ASP刺激的蛋白表达分别减少了47%Gβ(P<0.01),44%Gαq/11(P<0.05)、39%p-PKCα(P<0.05)和20%p-PKCζ(P>0.05);棕榈酸组也可观察到类似现象(P<0.05或P<0.01)。在前脂肪细胞,油酸仅抑制ASP刺激的p-PKCα和p-PKCζ(均P<0.05)蛋白表达;而棕榈酸下调上述4种信号蛋白的表达(P<0.05或P<0.01)。结论:油酸或棕榈酸抑制3T3-L1成熟脂肪细胞和前脂肪细胞ASP刺激的葡萄糖转运,证明FFA诱导脂肪细胞产生胰岛素抵抗状态下同时存在ASP抵抗。FFA诱导的ASP抵抗的发生机制与其干扰ASP-C5L2信号转导途径有关。ASP抵抗参与了'脂毒性'-胰岛素抵抗/肥胖症的病理生理过程。 | 温宇 Katherine Cianflone 胡秀芬 杨姗姗 卢慧玲 | 2010 | 中国病理生理杂志2010,26,4: | 4 |
| 15 | Long-term modifications of blood pressure in normotensive and spontane-ously hypertensive rats by gene delivery of rAAV-mediated cytochrome P450 arachidonic acid hydroxylase显示文摘Arachidonic acid cytochrome P-450 (CYP) hydroxylase 4A isoforms, including 4A1, 4A2, 4A3 and 4A8 in the rat kidney, catalyze arachidonic acid to produce 19/20-Hydroxyeicosatetraenoic acids (20-HETE), a biologically active metabolite, which plays an important role in the regulation of blood pressure. However, controversial results have been reported regarding the exact role of 20-HETE on blood pressure. In the present study, we used recombinant adeno- associated viral vector (rAAV) to deliver CYP 4A1 cDNA and antisense 4A1 cDNA into Sprague-Dawley (SD) rats and spontaneously hypertensive rats (SHR), respectively, to investigate the effects of long-term modifications of blood pressure and the potential for gene therapy of hypertension. The mean systolic pressure increased by 14.2±2.5 mm Hg in rAAV·4A1-treated SD rats and decreased by 13.7±2.2 mm Hg in rAAV·anti4A1-treated SHR rats 5 weeks after the injection compared with controls and these changes in blood pressure were maintained until the experiments ended at 24 weeks. In 4A1 treated animals CYP4A was overexpressed in various tissues, but preferentially in the kidney at both mRNA and protein levels. In anti-4A1-treated SHR, CYP4A mRNA in various tissues was probed, especially in kidneys, but 4A1 protein expression was almost completely inhibited. These results suggest that arachidonic acid CYP hydroxy- lases contribute not only to the maintenance of normal blood pressure but also to the development of hypertension. rAAV-mediated anti4A administration strategy has the potential to be used as targeted gene therapy in human hyperten- sion by blocking expression of CYP 4A in kidneys. | Fan ZHANG Chun Lian CHEN Jia Qing QIAN Jiang Tao YAN Katherine CIANFLONE Xiao XIAO Dao Wen WANG | 2005 | Cell Research2005,15,9: | 3 |
| 16 | A complement-dependent balance between hepatic ischemia/reperfusion injury and liver regeneration in mice显示文摘 | He Songqing Atkinson Carl Qiao Fei Cianflone Katherine Chen Xiaoping Tomlinson Stephen | 2009 | Journal of Clinical Investigation2009,,8: | 2 |
| 17 | 运动对糖尿病大鼠ASP和LPL的影响显示文摘研究运动对链脲佐菌素所致糖尿病大鼠LPL和ASP的影响。选用雄性SD大鼠,随机分为四组(每组10只),即:正常对照组,正常运动组,糖尿病模型组,糖尿病模型+运动组。运动组进行10 w的游泳训练。结果表明(1)糖尿病模型组与正常对照组大鼠相比,血浆ASP浓度、血糖、TG、和LDL明显升高,血清FFA有升高趋势,血浆LPL活性、血清胰岛素和ISI明显降低;(2)糖尿病模型+运动组较其非运动组血浆ASP浓度、血糖、TG、TC、FFA和LDL明显降低,血浆LPL活性、血清胰岛素和HDL含量明显升高。提示,糖尿病机体血浆ASP浓度升高,及其活性下降,同时伴有血浆LPL活性下降,使得FFA和富含TG的脂蛋白消除障碍,长期中等负荷运动可以降低血浆中ASP浓度,同时也可以增加ASP和LPL活性,进而降低FFA和TG水平,升高HDL,改善糖尿病机体的脂质代谢紊乱,预防其慢性并发症的发生。 | 张陵 景志强 张钧 Katherine Cianflone | 2007 | 西安体育学院学报2007,24,5: | 2 |
| 18 | 促酰化蛋白诱导的前脂肪细胞分化过程中转录因子表达的时序性研究显示文摘目的观察促酰化蛋白(ASP)诱导3T3-L1前脂肪细胞的分化过程,转录因子PPARγ、C/EBPδ、C/EBPαmRNA表达的强度及时序性。方法以3T3-L1前脂肪细胞为实验对象,用ASP代替经典激素鸡尾酒诱导刺激中的胰岛素,即促酰化蛋白、1-甲基-3-异丁基黄嘌呤和地塞米松(ASP+IBMX+DEX)诱导3T3-L1前脂肪细胞分化,分别在诱导分化1d、2d、4d、6d、8d收获细胞,采用RT-PCR法检测ASP诱导3T3-L1前脂肪细胞分化过程中转录因子PPARγ、C/EBPδ、C/EBPαmRNA表达的情况。结果PPARγmRNA在诱导分化1d时有低水平表达,在诱导分化过程中表达逐步升高,在终末分化阶段仍保持高水平表达。C/EBPδmRNA在诱导分化1d时有中等水平表达,在诱导分化2d时表达水平最高,诱导分化4d时表达明显减少,在诱导分化6d和8d,检测不到C/EBPδmRNA的表达。C/EBPαmRNA在诱导分化1d仅有低水平表达,在诱导分化过程中表达逐步升高,在终末分化阶段仍保持高水平表达。IBMX+DEX诱导前脂肪细胞分化过程中,PPARγ、C/EBPδ和C/EBPαmRNA分化早期也有一定升高,但明显低于ASP诱导的转录因子的表达。结论ASP对转录因子C/EBPδ、C/EBPα和PPARγ表达的时序性影响,可能是ASP诱导前脂肪细胞分化的重要分子机制之一。 | 王宏伟 卢慧玲 Katherine Cianflone 林汉华 | 2005 | 中国病理生理杂志2005,21,11: | 2 |
| 19 | 甲状腺功能异常对血浆脂肪细胞因子的影响显示文摘目的 研究甲状腺功能异常状态下脂肪细胞分泌的脂肪细胞因子在血浆中的变化, 从而了解甲状腺激素对脂肪细胞因子的影响。方法 甲状腺功能亢进组(甲亢组) 28 例, 男女各14 例, 甲状腺功能减退组(甲减组) 14例, 均为女性, 正常对照组30例, 男女各15例, 均空腹抽取肘正中静脉血, 测血脂、糖代谢指标及脂联素、促酰化刺激蛋白及补体C3水平。结果 与正常对照组比较, 甲亢组的脂联素水平明显升高, 促酰化刺激蛋白无明显差异,补体C3明显降低, 血脂水平明显降低, 游离脂肪酸明显升高, 空腹血糖及胰岛素也明显升高; 甲减组的体重指数增加, 血脂增加, 而其它指标均无明显变化。相关分析显示脂联素与甲状腺激素FT3、FT4 成正相关, 其它指标间均无明显的相关性。结论 甲状腺激素及甲亢状态可能促进脂联素的产生, 而甲亢状态下脂联素的产生机制尚有待进一步的研究。 | 余海英 张木勋 Katherine Cianflone 张建华 杨雁 王宏伟 卢慧玲 | 2005 | 华中科技大学学报(医学版)2005,34,2: | 2 |
| 20 | Circulating Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) Regulates VLDLR Protein and Triglyceride Accumulation in Visceral Adipose Tissue显示文摘 | Anna Roubtsova Mercedes Nancy Munkonda Zuhier Awan Jadwiga Marcinkiewicz Ann Chamberland Claude Lazure Katherine Cianflone Nabil G. Seidah Annik Prat | 2011 | Arteriosclerosis, Thrombosis, and Vascular Biology2011,,4: | 2 |